Project Abstract We are pleased to report that our Training Program has successfully trained graduate students who have become the next generation of creative independent investigators in the fields of gene regulation, mechanism of hormone and signal action, molecular genetics of development, homeostasis, metabolism and disease, inflammation, learning and neuronal function, global genomics and contemporary bioinformatics. This achievement reflects the strength of our training program fueled by its innovative, forward-thinking, and distinguished core faculty, who reflect the rich research environment of the La Jolla Mesa area that includes the UCSD School of Medicine, School of Biology, the Jacobs School of Engineering and the UCSD Program in Bioinformatics and Systems Biology. Notably, it also includes the Salk Institute for Biological Studies, The Scripps Research Institute, and the Sanford Burnham Prebys Medical Discovery Institute. Additionally, the recently constituted UCSD Institute for Genomic Medicine has further strengthened training in the contemporary fields of global genomics and chromatin biology. The core faculty are all internationally recognized for their research accomplishments and have strong records of training graduate students who have gone on to very productive academic and industry careers. Our program is highly interdisciplinary involving faculty from various Schools and Programs as well as the Salk Institute and The Scripps Research Institute. Graduate students are immersed in contemporary research approaches to important questions and have the full range of training in contemporary global genomics techniques, biochemistry, molecular biology, genetics, and gene regulation. Most importantly, students are expected to acquire a broad background of the scientific literature, and critical thinking, as well as the creative spirit that underlies success in these research areas. Formal coursework, hands-on bench experience, and intensive interaction and collaboration opportunities with program faculty will also prepare trainees for pursuing independent academic careers in these disciplines. We hope to be permitted the opportunity to continue this highly successful predoctoral training grant with a request for expansion for two postdoctoral trainees. Six predoctoral trainees per year are drawn from the highly competitive PhD programs. Candidates are chosen from more than 1000 applicants. Established criteria include research background, grade point average, GRE scores, and interviews with faculty and senior graduate students. All programs have a full complement of Diversity Initiatives. Trainees are directed towards careers in contemporary gene regulation, endocrinology, epigenomics, informatics, chromatin biology, metabolism and neurobiology, with a perspective towards translational application to human disease. Trainees are encouraged to develop skills in bench science, critical thinking, grantsmanship, teaching, and translational research in order to become independent investigators at leading academic institutions and make important contributions to biomedical science.